Bianco A W, Moore G E, Cooper B R, Taylor S D
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA.
Department of Veterinary Administration, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA.
J Vet Pharmacol Ther. 2018 Feb;41(1):98-104. doi: 10.1111/jvp.12425. Epub 2017 Jun 10.
Flunixin meglumine (FM) is a commonly used Nonsteroidal anti-inflammatory drug (NSAID) in horses, but clinical efficacy is often unsatisfactory. Ketorolac tromethamine (KT) demonstrates superior efficacy compared to other NSAIDs in humans, but its anti-inflammatory effects have not been investigated in the horse. Safety of repeated dosing of KT has not been evaluated. The first objective was to conduct a dose determination study to verify that a previously described dosage of KT would inhibit Lipopolysaccharide (LPS)-induced eicosanoid production in vitro, and to compare KT effects of this inhibition to those of FM. Then, a randomized crossover study was performed using nine healthy horses to evaluate plasma concentrations of KT and FM following IV administration. Administered dosages of KT and FM were 0.5 mg/kg and 1.1 mg/kg, respectively. Safety following six repeated doses of KT was assessed. Ketorolac tromethamine and FM suppressed LPS-induced Thromboxane B (TXB ) and Prostaglandin E (PGE ) production in vitro for up to 12 hr. Intravenous administration produced plasma concentrations of KT and FM similar to previous reports. No adverse effects were observed. A KT dosage of 0.5 mg/kg IV inhibited LPS-induced eicosanoids in vitro, and repeated dosing for up to 3 days appears safe in healthy horses. Investigation of in vivo anti-inflammatory and analgesic effects of KT is warranted.
氟尼辛葡甲胺（FM）是马匹中常用的非甾体抗炎药（NSAID），但其临床疗效往往不尽人意。酮咯酸氨丁三醇（KT）在人类中显示出比其他NSAID更优越的疗效，但其在马匹中的抗炎作用尚未得到研究。尚未评估重复给药KT的安全性。第一个目标是进行剂量测定研究，以验证先前描述的KT剂量是否能在体外抑制脂多糖（LPS）诱导的类花生酸生成，并将这种抑制作用的KT效果与FM的效果进行比较。然后，使用9匹健康马匹进行了一项随机交叉研究，以评估静脉注射后KT和FM的血浆浓度。KT和FM的给药剂量分别为0.5mg/kg和1.1mg/kg。评估了KT六次重复给药后的安全性。酮咯酸氨丁三醇和FM在体外抑制LPS诱导的血栓素B（TXB）和前列腺素E（PGE）生成长达12小时。静脉注射产生的KT和FM血浆浓度与先前报道相似。未观察到不良反应。静脉注射0.5mg/kg的KT剂量在体外抑制LPS诱导的类花生酸生成，并且在健康马匹中重复给药长达3天似乎是安全的。有必要对KT的体内抗炎和镇痛作用进行研究。
